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A transgenic zebrafish model for the in vivo study of the blood and choroid plexus brain barriers using claudin 5

机译:使用claudin 5进行体内血和脉络丛神经屏障体内研究的转基因斑马鱼模型

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The central nervous system (CNS) has specific barriers that protect the brain from potential threats and tightly regulate molecular transport. Despite the critical functions of the CNS barriers, the mechanisms underlying their development and function are not well understood, and there are very limited experimental models for their study. Claudin 5 is a tight junction protein required for blood brain barrier (BBB) and, probably, choroid plexus (CP) structure and function in vertebrates. Here, we show that the geneclaudin 5ais the zebrafish orthologue with high fidelity expression, in the BBB and CP barriers, that demonstrates the conservation of the BBB and CP between humans and zebrafish. Expression ofclaudin 5acorrelates with developmental tightening of the BBB and is restricted to a subset of the brain vasculature clearly delineating the BBB. We show thatclaudin 5a-expressing cells of the CP are ciliated ependymal cells that drive fluid flow in the brain ventricles. Finally, we find that CP development precedes BBB development and thatclaudin 5aexpression occurs simultaneously with angiogenesis. Thus, our novel transgenic zebrafish represents an ideal model to study CNS barrier development and function, critical in understanding the mechanisms underlying CNS barrier function in health and disease.
机译:中枢神经系统(CNS)具有特定的屏障,可保护大脑免受潜在威胁并严格调节分子运输。尽管中枢神经系统屏障起着至关重要的作用,但对其发展和功能的潜在机制仍知之甚少,并且对其进行研究的实验模型非常有限。 Claudin 5是脊椎动物的血脑屏障(BBB)和脉络丛(CP)结构和功能所需的紧密连接蛋白。在这里,我们显示了基因claudin 5ai在斑马鱼直系同源物中具有高保真度的表达,在BBB和CP屏障中,证明了人与斑马鱼之间BBB和CP的保守性。 claudin 5的表达与BBB的发育紧缩有关,并局限于清晰描述BBB的一部分脑血管。我们显示CP的claudin 5a表达细胞是纤毛的室管膜细胞,其驱动脑室中的流体流动。最后,我们发现CP的发展先于BBB的发展,claudin 5a的表达与血管生成同时发生。因此,我们新颖的转基因斑马鱼代表了研究中枢神经系统屏障发育和功能的理想模型,对于理解中枢神经系统屏障在健康和疾病中的作用机制至关重要。

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